A Phase 2a Study With Safety Run-in to Evaluate the Safety, Tolerability, and Preliminary Efficacy of FF-10832 Monotherapy or in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 23
- 主要终点
- Duration of Stable Disease in Combination Therapy
研究概览
简要总结
To confirm a recommended Phase 2 dose (RP2D) of FF-10832 (Gemcitabine Liposome Injection) given intravenously Day 1 of a 21-day cycle, in combination with 200 mg pembrolizumab given intravenously Day 1 of the same 21-day cycle, for treatment of advanced urothelial and non-small cell lung cancer
详细描述
This is a Phase 2a, open label clinical trial evaluating FF-10832 in combination with pembrolizumab and as monotherapy. The trial will begin with a safety run-in phase of 10 patients receiving combination therapy with pembrolizumab; FF 10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg).
After confirmation of the appropriate FF-10832 dose for use with pembrolizumab, the trial will enroll up to an additional 100 patients in 2 cohorts (urothelial cancer [UC] and non-small cell lung cancer [NSCLC]) into 4 separate expansion treatment arms (approximately 25 patients in each treatment arm). The disease-defined cohorts will be patients who have progressed on PD-1/PD-L1 therapy who have UC or NSCLC.
The UC cohort will be randomized (1:1) to one of two treatment arms (monotherapy or combination therapy) and the NSCLC cohort will be randomized (1:1) to one of two treatment arms (monotherapy or combination therapy), to further establish safety and gain preliminary information on antitumor activity of FF-10832 as monotherapy or in combination with pembrolizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent is provided by patient or legally acceptable representative;
- •Age ≥ 18 years;
- •Patient populations:
- •In the Safety Run-in, patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have disease progression after treatment with standard therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment or refuse standard treatment will be enrolled in therapy
- •In Expansion Phase, patient must have urothelial or NSCLC, and have failed prior anti-PD-1 or anti-PD-L1
- •Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
- •Eastern Cooperative Oncology Group performance status of 0 to 1
- •Life expectancy of ≥ 3 months
排除标准
- •Positive urine pregnancy test within 72 hours prior to treatment
- •Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 half-lives, whichever is shorter) prior to treatment;
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), AND was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event;
- •Has received prior radiotherapy within 2 weeks of start of study treatment.
- •For patients with NSCLC:
- •Patients who have received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of trial treatment are excluded;
- •Patients with mutations (e.g., EGFR mutations or ALK gene rearrangements) will be excluded unless they have been previously treated with all specific targeted therapies.
- •Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
- •Has had an allogeneic tissue /solid organ transplant.
研究组 & 干预措施
Safety Run-in Phase
FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
干预措施: Pembrolizumab (Drug)
Safety Run-in Phase
FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
干预措施: FF-10832 (Drug)
Urothelial Monotherapy - FF-10832 Expansion Phase
FF-10832 will be dosed at 40 mg/m2
干预措施: FF-10832 (Drug)
Urothelial Combination - FF-10832 + pembrolizumab Expansion Phase
FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
干预措施: Pembrolizumab (Drug)
Urothelial Combination - FF-10832 + pembrolizumab Expansion Phase
FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
干预措施: FF-10832 (Drug)
NSCLC Monotherapy - FF-10832 Expansion Phase
FF-10832 will be dosed at 40 mg/m2
干预措施: FF-10832 (Drug)
NSCLC Combination - FF-10832 + pembrolizumab Expansion Phase
FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
干预措施: Pembrolizumab (Drug)
NSCLC Combination - FF-10832 + pembrolizumab Expansion Phase
FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
干预措施: FF-10832 (Drug)
结局指标
主要结局
Duration of Stable Disease in Combination Therapy
时间窗: 7 years
To obtain a preliminary estimate of efficacy of the combination in expansion cohorts of patients with UC and NSCLC. Duration of Stable Disease is the length of time from the start of the treatment until the criteria for progression
Determine the incidence of Treament Emergent Adverse Events (TEAE)
时间窗: 7 years
Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs) and to confirm dose (RP2D) of FF-10832 given intravenously Day 1 of a 21 day cycle, in combination with 200 mg pembrolizumab, given intravenously Day 1 of the same 21-day cycle, for treatment of advanced solid tumors.
Duration of Stable Disease in Monotherapy
时间窗: 7 years
To obtain a preliminary estimate of efficacy of FF-10832 monotherapy in expansion cohorts of patients with urothelial cancer (UC) and non-small cell lung cancer (NSCLC). Duration of Stable Disease is the length of time from the start of the treatment until the criteria for progression are met
次要结局
- Overall Response Rate (ORR)(7 years)
- Determine Safety Profile of Combination Therapy(7 years)
- Progression-free survival (PFS)(7 years)
- Overall survival (OS)(7 years)
- Determine Safety Profile of Monotherapy(7 years)
- Duration of Response (DOR)(7 years)